title: Role of fibrinogen in acute ischemic kidney injury.
abstract: Renal ischemia-reperfusion (I/R) is associated with activation of the coagulation system and accumulation of blood clotting factors in the kidney. The aim of the present study was to examine the functional impact of fibrinogen on renal inflammation, damage, and repair in the context of I/R injury. In this study, we found that I/R was associated with a significant increase in the renal deposition of circulating fibrinogen. In parallel, I/R stress induced the de novo expression of fibrinogen in tubular epithelial cells, as reflected by RT-PCR, immunofluorescence, and in situ hybridization. In vitro, fibrinogen expression was induced by oncostatin M and hyper-IL-6 in primary tubular epithelial cells, and fibrinogen-containing medium had an inhibitory effect on tubular epithelial cell adhesion and migration. Fibrinogen(+/-) mice showed similar survival as wild-type mice but better preservation in early postischemic renal function. In fibrinogen(-/-) mice, renal function and survival were significantly worse than in fibrinogen(+/-) mice. Renal transplant experiments revealed reduced expression of tubular damage markers and attenuated proinflammatory cytokine expression but increased inflammatory cell infiltrates and transforming growth factor-β expression in fibrinogen(-/-) isografts. These data point to heterogeneous effects of fibrinogen in renal I/R injury. While a complete lack of fibrinogen may be detrimental, partial reduction of fibrinogen in heterozygous mice can improve renal function and overall outcome.
authors.affiliation: Department of Nephrology and Hypertension, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Sörensen-Zender
authors.forename: S
authors.initials: S
authors.lastname: Rong
authors.forename: N
authors.initials: N
authors.lastname: Susnik
authors.forename: J
authors.initials: J
authors.lastname: Lange
authors.forename: F
authors.initials: F
authors.lastname: Gueler
authors.forename: J L
authors.initials: JL
authors.lastname: Degen
authors.forename: A
authors.initials: A
authors.lastname: Melk
authors.forename: H
authors.initials: H
authors.lastname: Haller
authors.forename: R
authors.initials: R
authors.lastname: Schmitt
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology*; D000347:Afibrinogenemia / Q000503:physiopathology; D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism; D005340:Fibrinogen / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology; D016030:Kidney Transplantation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053683:Oncostatin M / Q000494:pharmacology; D015427:Reperfusion Injury / Q000503:physiopathology*
chemical_list: D015850:Interleukin-6; D053683:Oncostatin M; D005340:Fibrinogen
keywords: acute kidney injury; fibrinogen; ischemia-reperfusion; tubular expression